Flares Of Autoimmune Diseases Research Articles

Overview of acute liver failure in India.

Acute liver failure (ALF) is an infrequent, but serious complication subsequent to severe acute liver injury (sALI) due to various hepatotoxic agents such as hepatotropic virus(es) and drugs such as anti-tubercular medications, paracetamol, non-steroidal anti-inflammatory drugs (NSAIDs), antibiotics and anti-cancer and anti-epileptic therapy and due to metabolic and autoimmune disease flares. ALF after sALI presents with encephalopathy associated with prolonged international normalized ratio (INR). Mortality in ALF is high and ranges between 50% and 80%. Due to severe liver damage, multiple sequels consequent to hepatic dysfunction result in complications such as hyperammonemia that culminates in encephalopathy associated with cerebral edema; innate immune paralysis resulting in increased frequency of infections and endotoxemia causing decrease in systemic vascular resistance (SVR) and tissue hypoperfusion and damage-associated molecular patterns (DAMPs) released from damaged hepatic parenchyma inducing pro-inflammatory cytokine storm, which may cause other organ dysfunctions. Certain etiologies such as hepatitis E virus and hepatitis A virus-related ALF or paracetamol-ALF (hyper-acute presentation) have better survival than remaining causes. In addition, if etiology-specific treatment (antivirals for ALF related to hepatitis B virus (HBV) or Herpes simplex virus (HSV) or N-acetylcysteine for paracetamol) is available, then the outcome with treatment is better. About half of the patients can be salvaged with medical therapy. All patients need intensive care and organ support to provide time for the liver to regenerate. Various prognostic models to predict high probability of mortality have been described, which should be used to select patient early during the disease for liver transplantation, which is associated with high long-term survival in these sick patients. The Indian National Association for Study of the Liver (INASL) recommends the ALF-Early Dynamic (ALFED) model as a preferred prognostic model in the Indian scenario, where hepatitis viruses are a dominant etiology of ALF and occur on a naïve liver with good regenerative capacity.

Immune checkpoint inhibitor therapy in patients with cancer and pre-existing systemic sclerosis

ObjectiveImmune checkpoint inhibitor (ICI) therapies have dramatically improved outcomes in multiple cancers. ICI's mechanism of action involves immune system activation to augment anti-tumor immunity. Patients with pre-existing autoimmune diseases, such as systemic sclerosis (SSc), were excluded from initial ICI clinical trials due to concern that such immune system activation could precipitate an autoimmune disease flare or new, severe immune related adverse events (irAE). In the present study, we report our experience with ICIs in patients with pre-existing SSc. MethodsPatients with SSc who received ICI therapy for cancer were identified from the Johns Hopkins Scleroderma Center Research Registry. Through chart review and prespecified definitions, we identified whether patients experienced worsening SSc activity or new irAEs. SSc disease activity worsening was pre-defined as an increase in modified Rodnan skin score (mRSS), new scleroderma renal crisis, progression of interstitial lung disease (ILD) on CT scan, increased Raynaud's phenomenon frequency or severity, new pulmonary hypertension, or myositis flare. IrAEs also included active inflammatory arthritis and dermatitis. ResultsEight patients with SSc who received ICI therapy for cancer were included. Overall, SSc symptoms remained stable during and after ICI therapy. None of the patients with long-standing sine or limited cutaneous SSc (lcSSc) had progressive skin thickening after ICI therapy. One patient, who was early in his diffuse cutaneous SSc (dcSSc) disease course, experienced worsening skin thickening and renal crisis. Three patients (38 %) experienced a total of five irAEs (grade 2: diarrhea, mucositis and dermatitis; grade 3: pneumonitis, and grade 4: nephritis). The patient with grade 4 nephritis developed scleroderma renal crisis and immune checkpoint related nephritis simultaneously. There were no deaths due to irAEs. ConclusionIn this study, ICI therapy was well tolerated in patients with longstanding, sine or lcSSc. IrAE were common but generally manageable. Patients with early, active SSc may be at greater risk from ICI therapy, but more research is needed.

Management of autoimmune and viral hepatitis in immunotherapy: a narrative review.

Cancer immunotherapy has firmly established itself as a pillar of cancer care due to its advantages over traditional anti-tumor therapy but also carries limitations due to potential for severe adverse reactions. This review highlights the current understanding and management of patients with autoimmune and viral hepatitis immune in the setting of immune checkpoint inhibitor (ICI) therapy. A literature search was conducted on PubMed, Scopus, Google Scholar SEER*Stat databases (from inception to December 2022) using search terms: "immune checkpoint inhibitor", "autoimmune hepatitis", "viral hepatitis", "HBV pathogenesis", "HCV pathogenesis", "HBV reactivation", "HCV reactivation", "cancer immunotherapy", "immune related adverse events", "immune related hepatitis". Pre-existing autoimmune disease (AD), whether active or inactive, can predispose patients receiving ICI therapy to develop autoimmune disease flares or immune-related adverse events (irAEs). Thus, patients with AD have routinely been excluded from clinical trials and data on safety of ICI therapy are limited. Hepatic irAE can be seen in ICI therapy and is a distinct entity from autoimmune hepatitis (AIH). ICI therapy alters the immune environment in patients with chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infection. Patients who had prior exposure to HBV are at risk for viral reactivation. However, the prevalence of viral hepatitis in patients receiving immunotherapy is underrecognized and can lead to increases in liver biochemical tests as well as deterioration of liver function ultimately limiting treatment. The high morbidity and mortality associated with immune-related hepatitis emphasizes the need for screening of underlying diseases, including autoimmune and viral hepatitis, prior to initiation of ICI. Presence of AIH or chronic viral hepatitis is the most important risk factor for hepatic adverse events in ICI therapy. Screening for AIH, HBV and HCV is paramount in patients who will undergo ICI therapy.

P09 A catastrophic decline: a significant skin rash in a patient presenting with catastrophic antiphospholipid syndrome

P09 A catastrophic decline: a significant skin rash in a patient presenting with catastrophic antiphospholipid syndrome

Immunosuppressive therapy management in cancer patients with autoimmune diseases treated with immune checkpoint inhibitors: A case series and systematic literature review.

Prescribing immune checkpoint inhibitors (ICIs) to cancer patients with an autoimmune disease (AID) is presumed safe when cautious adverse event management is applied. However, guidelines on immunosuppressant (IS) adaptations are limited and real-world evidence is scarce. Current practice of IS adaptations is described in a case series of AID patients treated with ICIs in a tertiary university hospital in Belgium (1/1/2016-31/12/2021). Patient, drug and disease-related data were documented using retrospective chart review. A systematic search of the PubMed database was performed to identify similar cases (1/1/2010-30/11/2022). Sixteen patients were described in the case series (62% with active AID). Systemic IS were changed before ICI initiation in 5/9 patients. Four patients continued therapy, of which one achieved partial remission. Patients who had IS (partially) stopped before ICI start (n = 4) had AID flares in two cases; immune-related adverse events in three cases. In the systematic review, 37 cases were identified in 9 articles. Corticosteroids (n = 12) and non-selective IS (n = 27) were continued in, respectively, 66% and 68% of patients. Methotrexate was frequently discontinued (13/21). Biologicals, excluding tocilizumab and vedolizumab, were withheld during ICI treatment. Out of all patients with flares (n = 15), 47% had stopped IS therapy before ICI start and 53% had continued their AID drugs. A detailed overview of IS management in patients with AID receiving ICI therapy is presented. Expanding the knowledge base germane to IS management with ICI therapy in the diverse population is essential to evaluate their mutual impact, thus advancing responsible patient care.

Immune-related adverse events after immune checkpoint inhibitor exposure in adult cancer patients with pre-existing autoimmune diseases.

Immune checkpoint inhibitor (ICI) therapy can predispose patients to immune-related adverse events (irAEs) and autoimmune disease (AD) flare-ups, but the characteristics of irAEs among patients with pre-existing ADs are largely unknown. We conducted this study to determine the clinical courses, irAEs, AD flares, treatment, and outcomes of patients with AD on ICIs. This was a retrospective study of adult cancer patients at a large cancer center who were diagnosed with ADs before undergoing ICI therapy. Patients' clinical courses, complications, treatments, and outcomes related to both ADs flares and irAEs were collected and analyzed. The study included 197 patients. Most (55.4%) were women. Melanoma comprised the highest proportion (28.4%) of malignancies, and most (83.8%) patients received PD-1/PD-L1 inhibitors. Fifty (25.3%) patients developed a new irAE after starting ICI therapy, while 29 (14.7%) patients had an AD flare-up. Patients with inflammatory bowel disease had the highest incidence of AD flare-ups (31.7%), while patients with Hashimoto hypothyroidism had the highest incidence of new irAEs (39.2%). Patients with inflammatory bowel disease had more severe adverse events. In our cohort, patients with a new diagnosis of irAE were treated with immunosuppressive therapy. AD flares were managed similarly. With regard to irAE manifestations, the most common presentations were colitis (24 [12.1%] patients), hepatic transaminase elevations (8 [4%] patients), and pneumonitis (7 [3.5%] patients). Our findings suggest that patients with gastrointestinal and rheumatologic ADs had a higher incidence of AD flare-ups, while patients with Hashimoto hypothyroidism and neurologic ADs had a higher incidence of new irAEs. Patients with prior ADs experiencing flare-ups or new irAEs after ICI therapy tend to require aggressive immunosuppressive treatment. Thorough evaluation of baseline disease status, appropriate medical management before ICI therapy, and early recognition of inflammatory exacerbation may help ensure long-term success in treating and improving outcomes in these patients.

Infectious diseases, autoantibodies, and autoimmunity

Infections are known to trigger flares of autoimmune diseases in humans and serve as an inciting cause of autoimmunity in animals. Evidence suggests a causative role of infections in triggering antigen-specific autoimmunity, previous thought mainly through antigen mimicry. However, an infection can induce bystander autoreactive T and B cell polyclonal activation, believed to result in non-pathogenic and pathogenic autoimmune responses. Lastly, epitope spreading in autoimmunity is a mechanism of epitope changes of autoreactive cells induced by infection, promoting the targeting of additional self-epitopes. This review highlights recent research findings, emphasizes infection-mediated autoimmune responses, and discusses the possible mechanisms involved.

S963 Characteristics, Treatment and Outcome of Patients With Previously Diagnosed Autoimmune Disease After Immune Checkpoint Inhibitor Exposure

Introduction: Immune checkpoint inhibitors (ICI) can predispose to immune related adverse events (irAEs) and autoimmune disease (AD) flare-ups. irAE characteristics among patients with previously diagnosed AD have not been well studied. We aim to describe the clinical course, complications, treatment, and outcomes of patients with AD on ICIs. Methods: This is a retrospective chart review of adult cancer patients at the MD Anderson Cancer Center diagnosed with AD (based on ICD code) prior to the first dose of ICI treatment between 01/01/2010 and 04/30/2021. Patients’ clinical course, treatment and outcomes related to both AD and irAE were collected and analyzed. Results: A total of 197 patients were included in this study. A majority of our sample were female (55.4%) most frequently having melanoma (28.4%) and receiving PD-1/L1 inhibitors (83.7%). Forty-two patients (21.3%) developed a new irAE after starting immunotherapy, while 29 had an AD flare (14.7%). Patients with inflammatory bowel disease (IBD) had the highest rate of AD flare (31.7%), while patients with hypothyroidism had the highest incidence of new irAEs at 39.2%. Patients with IBD had more severe adverse events however with a median CTCAE grade of 3.5. In our cohort, all patients that were diagnosed with a new irAE were treated with immunosuppressive therapy. AD flares were managed similarly. With regards to irAE manifestations, colitis was the most common presentation in our cohort; at least 24 patients (23.2%) excluding those patients with a diagnosis of (IBD and microscopic colitis) had this type of complication. This was followed by pneumonitis in 9 patients (4.5%) and transaminitis in 7 patients (3.5%). Conclusion: Studies on the correlation between prior AD and immunotherapy are still lacking. Our findings suggest that patients with GI and rheumatologic ADs had higher incidence of AD flare up than new irAE development, while patients with thyroid and neurologic ADs appeared to have higher incidence of new irAEs compared to AD flare. Patients with prior AD experiencing a flare or a new irAE after immunotherapy tend to require more aggressive immunosuppressive treatment for symptom control. Thorough evaluation of baseline disease status, the appropriate medical management prior to ICI, and early recognition of inflammatory exacerbation could be key factors to ensure long-term success with treating and improving outcomes of these patients. Table 1. - Summary of irAE characteristics per Autoimmune Disease system, N=197 Autoimmune Disease per system Active AD status before ICI, N (%) On medical Rx before ICI, N (%) Flare up after ICI, N (%) Type of ICI Peak CTCAE grade of flare up (median, IQR) Required IMS for flare up, N (% of those that had flare) New irAE in different organ from AD, N (%) Peak CTCAE of irAE (median, IQR) IMS required for irAE, N (% of those that had irAE) Hematological ITP (N=2) 0 (0) 0 (0) 0 (0) PD1/L1=2 (100) N/A N/A 0 (0) N/A N/A Endocrine Hypothyroidism (N=51) 0 (0) 51 (100) 2 (3.9) Combined= 9 (17.6); PD1/L1=42 (82.3) Grade 2 in 1 (50) 0 (0) 20 (39.2) 2(1-3) 20 (100) Neurological MS-TM-GBS (N=27) 27 (100) 3 (11.1) 2 (7.4) Combined= 1 (3.8); PD1/L1= 21 (77.7); CTLA-4=5 (18.5) N/A 2 (100) 5 (18.5) 1(1-1.5) 5 (100) Rheumatological Rheumatoid A (N=58) 0 (0) 58 (100) 15 (25.8) Combined= 1 (1.7); PD1/L1= 57 (98.2); N/A 15 (100) 12 (20.6) 2.5(2-3) 9 (75) Gastroenterological (N=30) 0 (0) 30 (100) 10 (33.3) Combined=3 (10); PD1/L1=27 (90) N/A 10 (100) 5 (16.6) N/A 5 (100) Microscopic Colitis (N=10) 0 (0) 3(30) 8 (80) PD1/L1=10 (100) N/A 8 (100) 1 (10) N/A 1 (100) Celiac Disease (N=1) 0 (0) 0 (0) 0 (0) PD1/L1=1 (100) N/A N/A 0 (0) N/A N/A IBD (N=19) 1 (5.2) 10 (52.6) 6 (31.7) Combined=3 (15.7); PD1/L1=16 (84.2) N/A 6 (100) 4 (21) 3.5(3-4) 4 (100) Footnote: IMS=immunosuppressant. ITP=Immune Thrombocytopenic Purpura. MS=Multiple Sclerosis. TM= Transverse Myelitis. GBS=Guillain Barre Syndrome. IBD=Inflammatory Bowel Disease.*all the patients had baseline low activity at the time of ICI initiation. Flare up occurred when the symptoms progressed from baseline activity.

Azathioprine-induced hypersensitivity reaction mimicking sepsis in a patient with systemic lupus erythematosus.

A 21-year-old woman with a history of systemic lupus erythematosus presented to the emergency department with acute-onset nausea, vomiting, and fevers. Two weeks prior, she was started on azathioprine 50 mg daily by her outpatient rheumatologist; the dose was up-titrated to 100 mg when repeat blood work showed no drug toxicity. The morning after increasing her dose, she was awoken by recurrent emesis. At presentation, she was febrile, tachycardic, and hypotensive. Her exam showed mild, generalised abdominal tenderness but was otherwise unremarkable. Lab work demonstrated elevated inflammatory markers, elevated liver transaminases, and stable hypocomplementemia. Chest X-ray and computed tomography abdomen/pelvis were unrevealing. She was given intravenous fluids and broad-spectrum antibiotics, and azathioprine was held. A thorough infectious workup returned negative. A flare of her systemic lupus erythematosus was considered but deemed an unlikely explanation of her systemic inflammatory response syndrome. With azathioprine discontinuation, she made a rapid, near-complete recovery within 24 h of admission, suggesting a diagnosis of azathioprine hypersensitivity syndrome. This case exemplifies the difficulty in distinguishing azathioprine hypersensitivity from mimickers such as infection and underlying autoimmune disease flare. Prompt recognition of hypersensitivity can lead to appropriate discontinuation of the drug and prevent future morbidity.

Multidisciplinary approach to treatment with immune checkpoint inhibitors in patients with HIV, tuberculosis, or underlying autoimmune diseases.

We reviewed the available information on the use of immune checkpoint inhibitors (ICIs) in populations with special conditions, namely, patients with HIV, tuberculosis, or underlying autoimmune disease. Available data show that treatment with ICIs is safe in patients with HIV; it is advisable, however, that these patients receive adequate antiretroviral therapy and have an undetectable viral load before ICIs are initiated. Tuberculosis reactivation has been reported with the use of ICIs, possibly due to immune dysregulation. Tuberculosis has also been associated with the use of immunosuppressors to treat immune-related adverse events (irAEs). Active tuberculosis must be ruled out in patients with symptoms or signs, and selected patients may benefit from screening for latent tuberculosis infection, although more data are required. Limited data exist regarding the safety of ICIs in patients with cancer and autoimmune disease. Data from observational studies suggest that up to 29% of patients with a preexisting autoimmune disease treated with an ICI present with an autoimmune disease flare, and 30% present with a de novo irAE of any type. The frequency of flares appears to differ according to the type of ICI received, with higher rates associated with PD-1/PD-L1 inhibitors. The most common autoimmune diseases for which patients reported flares with ICI therapy are rheumatoid arthritis, other inflammatory arthritis, and psoriasis. Most studies have reported flares or de novo irAEs associated with ICIs that were mild to moderate, with low rates of discontinuation and no deaths due to flares. Therefore, the use of ICIs in these patients is possible, but careful monitoring is required.

A Self-Resolving Flare of Psoriasis after COVID-19 Vaccination

Flares of autoimmune disorders have been rarely reported after COVID-19 infection as well as vaccinations. The authors report a case of psoriasis flare after COVID-19 vaccination, which was successfully treated with topical steroids. This case illustrates that although autoimmune disease flares might be seen post-vaccination, they are usually mild and self-resolving. Therefore, based on overall safety and efficacy, COVID-19 vaccination is strongly encouraged in vulnerable patient populations.

The impact of pembrolizumab on patients with pre-existing autoimmune diseases.

2660 Background: Immune checkpoint inhibitors (ICI) have changed the therapeutic landscape across a range of solid and hematologic malignancies. With the mechanistic activation of the adaptive immune response and known unique development of immune-related adverse effects (irAE), there is a theoretical risk of causing detrimental effects on patients with pre-existing autoimmune diseases (AID). However, this patient population was excluded from many clinical trials, and there is limited and conflicting retrospective data speculating upon the impacts of using ICI therapy in patients with AID. This study aims to report the impact of pembrolizumab in patients with AID. Methods: Patients who received pembrolizumab for treatment of any type of cancer between 1/1/2017-8/1/2021 were retrospectively reviewed, and patients with AID (rheumatologic or non-rheumatologic) were identified. Data including age, gender, race, ECOG, and primary cancer diagnosis were collected. AID was characterized by type, activity (symptomatic vs. asymptomatic at ICI initiation), and immunosuppressive treatment (IST) use. Outcomes included flare of AID, irAE, and ICI discontinuation. Results: Out of 810 patients, 12 with pre-existing AID were found and being treated for non-small cell lung cancer (NSCLC) (58% N=7), renal cell carcinoma (RCC) (16.6% N=2), colorectal cancer (CRC) (8% N=1), head and neck cancer (8% N=1), and cervical cancer (8% N=1). Around 67% of these patients were females with a median age of 65 years (50-77). Median ECOG was 1 (0-2). 9 patients (75%) had rheumatologic disease (5 rheumatoid arthritis (RA), 1 systemic lupus erythematosus (SLE), 2 psoriatic arthritis, and 1 systemic sclerosis (SS)). 3 patients (25%) had non-rheumatologic AID (1 multiple sclerosis (MS), 1 autoimmune hepatitis, and 1 Evan’s syndrome). All patients were asymptomatic prior to initiation of therapy. At the time of ICI initiation, 11 patients (92%) were on therapy, including steroids, methotrexate, and other IST. Due to concern for severe flare, pembrolizumab was discontinued in 3 (25%) MS, RA, and SS patients treated for RCC, CRC, and NSCLC, respectively. 3 patients (25%) developed irAE unrelated to their AID (pneumonitis, dermatitis, arthritis, gastritis) and received steroids. 4 patients (33.3%) had documented flares while on pembrolizumab requiring escalation of their ongoing therapy, and 1 NSCLC patient had a severe exacerbation of SS requiring cyclophosphamide and rituximab infusions. Conclusions: This analysis adds to the limited available literature that patients with an AID and on IST appear to have minimal AID-associated flares requiring intervention and tolerate pembrolizumab with a similar rate of irAE compared to patients without AID. Additional larger studies are needed to assess the efficacy of treatment in this population.

AB1138 SAFETY OF SARS - COV- 2 VACCINES IN PATIENTS WITH AUTOIMMUNE DISEASES

BackgroundPatients (pts) with autoimmune diseases are at higher risk of infections, including those by SARS-COV-2. There is no general agreement regarding priority criteria for anti-COVID vaccine access for pts with autoimmune rheumatic diseases (ARD). Few studies have addressed the issue of anti-COVID vaccination in these pts, but many are available on the safety, immunogenicity, efficacy, and possible contraindications of traditional vaccines in pts with ARD. These studies may represent the basis on which to recommend the anti-COVID-19 vaccines.ObjectivesPatients (pts) with autoimmune diseases are at higher risk of infections, including those by SARS-COV-2. There is no general agreement regarding priority criteria for anti-COVID vaccine access for pts with autoimmune rheumatic diseases (ARD). Few studies have addressed the issue of anti-COVID vaccination in these pts, but many are available on the safety, immunogenicity, efficacy, and possible contraindications of traditional vaccines in pts with ARD. These studies may represent the basis on which to recommend the anti-COVID-19 vaccines.MethodsA telephone survey investigating the AE of SARS-CoV-2 vaccinations on pts with systemic lupus erythematosus, systemic sclerosis, inflammatory arthritis (rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis), idiopathic inflammatory myopathies, ANCA-associated vasculitis was administered. Data extraction included diagnosis, disease activity status, demographics, disease duration, therapy, comorbidities, and laboratory tests. Vaccinated participants are asked to report whether they experienced any local or systemic AE following vaccination, and if so, to report on the severity and duration of the AE. Mild AE were defined as unpleasant reactions that did not limit daily activities, moderate AE as those that limited daily activities, and severe AE - required medical attention. Serious AE were defined as reactions that resulted in hospital admission.ResultsChAdOx1 nCoV-19 and BNT162b2 are the most common vaccines in our pts. 98 (39,84 %) of 246 pts received the BNT162b2 vaccine, 95 (38,62 %) - ChAdOx1 nCoV-19 vaccine, 47 (19,10%) - CX-024414 and 6 (2,44 %) were vaccinated with Ad26.COV2-S. 127 (51,63%) pts had at least one mild AE and 51 (20,73 %) pts reported moderate AE. Severe AE were rare - 4 (1,63 %) pts and no serious AE were reported. The most commonly reported AE is pain (40,24 %), redness (30,49 %), swelling (18,7 %) at the injection site, which was consistent across all vaccines for both first and second doses. Systemic AE occurred in 104 (43,27 %) pts, most frequently fatigue (29,67 %), headache (27,13 %) and muscle ache (24,39 %). The symptoms started mostly during the first day post-vaccination and lasted for no more than two days. Joint complaints were reported in 8,94 %, but only a small proportion of pts (2,84 %) reported a deterioration of their autoimmune disease up to 3 months after COVID-19 vaccination. Age was a significant effect modifier in the association between autoimmune status and the risk of moderate or severe AE. Vaccination with ChAdOx1 nCoV-19, female sex, age between 35 - 50 years were independently associated with an increased likelihood of reporting any AE. The current results support the safety of different COVID-19 vaccines in pts with ARD. This information can help fight vaccine hesitancy in this population.ConclusionOur data indicated that COVID-19 vaccines are well tolerated by pts with ARD. We did not observe any serious AE, but the number of pts included in our study is too low to draw conclusions about rare serious events. Additionally, our data suggest that COVID-19 vaccinations do not seem to trigger autoimmune disease flares, which is in accordance with data from previous small studies that assessed consequences of vaccines in pts with ARD.Disclosure of InterestsNone declared

Safety of the BNT162b2 mRNA COVID-19 vaccine in patients with familial Mediterranean fever.

ObjectivesEvidence suggests a possible association between the COVID-19 vaccine and autoimmune disease flares or new onset of various autoinflammatory manifestations, such as pericarditis and myocarditis. The objective of this study was to assess the safety of an mRNA-based BNT162b2 anti-COVID-19 vaccine in individuals with FMF, a prototypic autoinflammatory disease.MethodsPatients participating in this study fulfilled the criteria for diagnosis of FMF, were older than 18 years and received at least one dose of the vaccine. Data on baseline characteristics, features of FMF, post-vaccination side effects, and disease flares were acquired using electronic medical files and telephone interviews.ResultsA total of 273 FMF patients were recruited for the study. >95% were vaccinated with two doses of the vaccine. The rates of local reactions following the first and second vaccine doses were 65.5% and 60%, respectively, and 26% and 50.4%, respectively, for systemic adverse events. These rates are lower than those reported for the general population from real-world and clinical trial settings. Postvaccination FMF activity remained stable in most patients. None of the patients reported an attack of pericarditis or myocarditis, considered the most serious vaccine-associated adverse events. Patients with a more active FMF disease and patients harboring the M694V mutation had a significantly higher rate of post-vaccination systemic side effects and attacks.ConclusionThe BNT162b2 mRNA COVID-19 vaccine is safe in patients with FMF. Our results support the administration of this vaccine to FMF patients according to guidelines applicable to the general population.

Safety of immune checkpoint inhibitors in patients with cancer and pre-existing autoimmune disease.

BackgroundPatients with pre-existing autoimmune disease (AD) have been largely excluded from clinical trials of immune checkpoint inhibitors (ICI), so data on safety of ICIs among patients with pre-existing AD are relatively limited. There is a need for deeper understanding of the type and management of complications from ICI in patients with pre-existing AD. We sought to investigate the safety of ICIs in patients with pre-existing ADs as well as factors associated with AD flare.MethodsConsecutive patients with pre-existing AD who received monotherapy as well as combination of ICI therapies at our institution from September 2015 through September 1st, 2018 were identified. Clinical information was abstracted via manual chart review. Clinical factors associated with AD flare were determined using multivariable logistic regression.ResultsA total of 42 patients were identified of whom 12 developed AD flare. All flares were treated with oral or topical corticosteroids, while a patient with flare of rheumatoid arthritis was treated with tofacitinib and another patient with Crohn’s flare was treated with infliximab. Female sex, smoking status, higher age at the start of ICI therapy, cancer type, such as melanoma and lung cancer as compared to other cancers, were not significantly associated with AD flare, however, patients with underlying rheumatologic AD were noted to have a five times greater likelihood of flare as compared to other non-rheumatologic AD. Nine patients developed new immune related adverse events (IRAEs) unrelated to underlying AD, such as inflammatory poly-arthropathy, neuropathy, hypothyroidism, diarrhea, lichenoid drug eruptions, which were managed with oral and/or topical corticosteroids. ICI was stopped in six patients due to AD flare, in four patients due to IRAE flare (out of which one resumed ICI after resolution of IRAE).ConclusionsIn patients with pre-existing AD treated with ICI, AD flare occurred in 28% of patients and were managed successfully with corticosteroids alone or with additional disease-modifying therapies. ICI could be considered in patients with AD, but with very close monitoring and preemptive multidisciplinary collaboration.

The safety and efficacy of immune-checkpoint inhibitors in patients with cancer and pre-existing autoimmune diseases.

Objective: This study aims at investigating the safety and efficacy of immune-checkpoint inhibitors (ICIs) in patients with cancer and pre-existing autoimmune disease (AID). Materials & methods: PubMed, Embase and Cochrane Library were searched for relevant studies. The primary end points of the study were immunotoxicity and cancer response. Results: At the early use of ICIs, compared with those with active AID, grade 3-4 AID flare occurred more frequently in patients with inactive AID after treatment with ICIs; and the incidence of grade 3-4 immunotoxic effects was significantly lower in patients undergoing immunosuppressive therapy than those without corresponding treatment. In addition, patients with worsening AID generally obtained a better objective response than those without a flare. Conclusion: This study demonstrates that the toxic effects induced by immunotherapy are generally manageable in patients with cancer and pre-existing AID, some of whom even achieve satisfactory antitumor effects in clinical practice.

31P Safety and efficacy of immune checkpoint inhibitors in cancer patients with pre-existing autoimmune disease: A UK tertiary cancer centre experience

Immune check-point inhibitors (ICPi) are routinely used in cancer treatment in the United Kingdom and are associated with immune-related adverse events (irAE). Most patients with autoimmune disease (AID) are often excluded from clinical trials investigating ICPi, due to hypothetical increased risks of AID flare or severe irAE, but these risks have never been conclusively verified. We present experience using ICPi at a UK tertiary cancer centre, comparing the irAE profile and efficacy in patients with pre-existing AID to those without. This was a single centre retrospective analysis of electronic records of solid tumour patients who received treatment with an ICPi from January 2017 to December 2020. From a total of 562 patients, 15 had pre-existing AID. These were compared to those without AID in a 1:3 matched cohort for tumour-type and treatment. The AID cohort had inflammatory bowel disease (N=5), psoriasis (N=3), rheumatoid arthritis (N=2), polymyalgia rheumatica (N=2), autoimmune endocrinopathies (N=4), lupus (N=1) and sarcoidosis (N=1). 3 patients had 2 co-existing AID. All 15 patients had well controlled AID. 9 were on hormone replacement, immunosuppressive (prednisolone <10mg, n=2, mesalazine, n=1), or topical agents. 6 were not on AID treatment. The table below lists patient demographics, irAE and outcomes. 3 out of 15 AID patients had irAE possibly linked to their underlying AID (1 psoriasis, 1 RA, 1 colitis; no G3 or higher). No significant differences were found in the number of G3 or higher irAE, treatment discontinuation due to irAE, response to treatment, or survival between cohorts.Table: 31PPatient demographics, irAE and outcomesNo AID (n=45)AID (n=15)P-valueTumour type0.9698Gynaecological31Colorectal62Head & neck31Merkel cell31Urothelial62Non-small cell lung248Immunotherapy agent>0.9999Atezolizumab31Pembrolizumab279Durvalumab31Nivolumab62Ipilimumab and nivolumab62Treated under clinical trial0.8686Yes134No3211Total number of irAEs0.569102191175271Grade 3-5 irAEs0.42Grade 3 or 481Grade 510Best response0.1044Stable disease51Mixed response51Complete or partial response185Progressive disease144 Open table in a new tab Exacerbation of pre-existing AID was infrequent and did not result in severe toxicity. Patients with well-controlled AID could be considered for entry in clinical trials involving ICPi.

Macrophage activation syndrome in a young adult patient with a background of systemic lupus erythematosus: a case report

Background: Macrophage activation syndrome (MAS) is a rare but potentially life-threatening condition associated with systemic lupus erythematosus (SLE), as well as several other autoimmune conditions. Case Presentation: We present a case of MAS in a 30-year-old patient with a background of SLE presenting with persistent fever and hemodynamic instability. Broad-spectrum antibiotics were initially started for possible sepsis of unknown origin, but a lack of response or evidence of an infection source led to further laboratory investigations and additional diagnostic imaging. Hyperferritinemia, a low fibrinogen, hypertriglyceridemia, and pancytopenia raised the suspicion of MAS. Echocardiography revealed a pericardial effusion requiring pericardiocentesis. With rapid disease progression, multiorgan failure ensued, and shortly after a high dose, methylprednisolone was commenced; the patient&amp;apos;s condition worsened and she died after a cardiac arrest. Conclusion: This case highlights the challenges involved in diagnosing MAS and in differentiating it from more common presentations such as sepsis or autoimmune disease flares, and demonstrates the possible rapid disease progression. Therefore, early recognition of certain clinical features and laboratory markers are essential to enable early diagnosis, commencement of immunosuppressive treatment, and to ultimately improve outcomes in such critically unwell patients.

COVID-19 and autoimmune diseases.

Purpose of reviewThe aim of this study was to evaluate the relationship between infection with SARS-CoV-2 and autoimmunity.Recent findingsCoronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome (SARS) associated coronavirus 2 (SARS-CoV-2). Although most of the infected individuals are asymptomatic, a proportion of patients with COVID-19 develop severe disease with multiple organ injuries. Evidence suggests that some medications used to treat autoimmune rheumatologic diseases might have therapeutic effect in patients with severe COVID-19 infections, drawing attention to the relationship between COVID-19 and autoimmune diseases. COVID-19 shares similarities with autoimmune diseases in clinical manifestations, immune responses and pathogenic mechanisms. Robust immune reactions participate in the pathogenesis of both disease conditions. Autoantibodies as a hallmark of autoimmune diseases can also be detected in COVID-19 patients. Moreover, some patients have been reported to develop autoimmune diseases, such as Guillain--Barré syndrome or systemic lupus erythematosus, after COVID-19 infection. It is speculated that SARS-CoV-2 can disturb self-tolerance and trigger autoimmune responses through cross-reactivity with host cells. The infection risk and prognosis of COVID-19 in patients with autoimmune diseases remains controversial, but patient adherence to medication regimens to prevent autoimmune disease flares is strongly recommended.SummaryWe present a review of the association between COVID-19 and autoimmune diseases, focusing on similarities in immune responses, cross-reactivity of SARS-CoV-2, the development of autoimmune diseases in COVID-19 patients and the risk of COVID-19 infection in patients with preexisting autoimmune conditions.

Granulomatosis with polyangiitis in a patient treated with dabrafenib and trametinib for BRAF V600E positive lung adenocarcinoma

BackgroundDabrafenib and trametinib combination therapy is approved for the treatment of patients with BRAF V600E positive tumors including melanoma and lung cancer. The effect of BRAF and MEK inhibitors on the immune system is not fully understood although a number of case reports indicate autoimmune side effects related to the use of these drugs. Here, we discuss a case of a patient diagnosed with granulomatosis with polyangiitis (GPA) shortly after starting treatment with dabrafenib and trametinib for BRAF V600E positive metastatic lung adenocarcinoma.Case presentationA 57 years old female patient was diagnosed with recurrent lung adenocarcinoma following initial lobectomy for early stage disease. A BRAF V600E mutation was identified at the time of recurrence and she received combination dabrafenib and trametinib therapy. Shortly after commencement of treatment, she developed persistent fevers necessitating withholding both drugs. Pyrexia continued and was followed by left vision loss and acute kidney injury. Further rheumatological workup led to the unifying diagnosis of GPA. The patient was then treated with rituximab for GPA to the present date while all antineoplastic drugs were held. Lung cancer oligoprogression was addressed with radiation therapy and has not required further systemic treatment whereas GPA has been controlled to-date with rituximab.ConclusionsThis case report raises awareness among clinicians treating patients with lung cancer for the possibility of triggering a flare of autoimmune diseases like GPA in patients with BRAF V600E positive lung cancer receiving treatment with BRAF directed therapy.